It is an aim of the proposed project to develop a quantitative and qualitative assay for human hemopoietic pluripotent stem cells and leukemic stem cells in mice since no assay for human pluripotent hemopoietic stem cells is available to date. Such an assay would enable us to evaluate differences between normal and leukemic stem cells, to quantitate their coexistence in relapse and remission of the disease, to determine the responsiveness of the leukemic population to different regimens of chemotherapy, to determine the nature of defects in cases of various hematologic disorders and immune deficiency diseases. The possibility to evaluate and enumerate human pluripotent hemopoietic stem cells is of obvious importance not only to many hematologic disorders, but also in the field of bone marrow transplantation, since by extrapolation from extensive mouse data, these cells generate all different hemopoietic cell lines, including lymphoid line. Little is known about sequential steps in differentiation of human hemopoietic stem cells into myeloid, erythroid or lymphoid progenitors, and of these cells into a large number of mature and extremely specialized functional elements. Our experiments are designed to identify some of these steps and their controlling mechanism. If hemopoietic replacement should become a therapeutic procedure in treatment of human disease, then it is necessary to understand and be able to control these individual steps. The mouse model has been chosen for growth of human hemopoietic stem cells for the following reasons: (1) The spleen colony technique for quantitation of hemopoietic stem cells is available; (2) a substantial body of information on hemopoiesis has been accumulated for this species; (3) there are available strains of mice which are either "nonresponders" or poor responders to xenogeneic bone marrow grafts as well as immunodeficient mice which can allow the growth of human marrow cells.